Cancer-related changes and low-to-moderate exposure to welding fumes: A longitudinal study

OBJECTIVE: This study tested for an association between early cancer-related biomarkers and low-to-moderate exposure to fumes from welding mild steel. METHODS: Male, non-smoking participants from southern Sweden were recruited and examined (N=338, 171 welders and 167 controls); of these, 78 welders and 96 controls were examined on two occasions six years apart. Exposure to welding fumes was evaluated by measuring respirable dust, welding years, and cumulative exposure. DNA methylation of CpG sites within the cancer-related genes AHRR, F2RL3, and B3GNTL1 was measured by pyrosequencing and relative mitochondrial DNA copy number and telomere length were measured by qPCR in whole-blood samples. Multivariate models were used for longitudinal analysis. RESULTS: Median exposure to respirable dust was 0.7 mg/m(3) at both timepoints, adjusted for use of personal protective equipment. Compared with controls, welders showed a significant decrease over time in DNA methylation of B3GNTL1 CpG1 and CpG4 [adjusted for age, body mass index, and smoking: β=-0.66, standard error (SE)=0.28; β=-0.48, SE=0.24, respectively]. In addition, exposure to respirable dust and cumulative exposure was associated with a decrease in methylation of F2RL3 CpG2 among all welders (adjusted β=-0.67, SE=0.23 and β=-0.03, SE=0.02, respectively). No significant associations were found for AHRR, mitochondrial DNA copy number, or telomere length. CONCLUSION: Low-to-moderate exposure to welding fumes was associated with a small effect on selected early epigenetic biomarkers of cancer. The direction of the methylation pattern (lower methylation of specific CpG sites) indicates early lung cancer-related changes associated with mild steel welding.